Wednesday, September 17, 2025
NIH-funded study reveals brain changes long before chronic traumatic encephalopathy (CTE) develops.
Research supported by the National Institutes of Health (NIH) shows that repeated head impacts from contact sports can cause early and lasting changes in the brains of young- to middle-aged athletes. The findings show that these changes may occur years before chronic traumatic encephalopathy (CTE) develops its hallmark disease features, which can now only be detected by examining brain tissue after death.
“This study underscores that many changes in the brain can occur after repetitive head impacts,” said Walter Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “These early brain changes might help diagnose and treat CTE earlier than is currently possible now.”
Scientists at the Boston University CTE Center, the U.S. Department of Veterans Affairs Boston Healthcare System and collaborating institutions analyzed postmortem brain tissue from athletes under age 51. Most of them had played American football. The team examined brain tissue from these athletes, using cutting-edge tools that track gene activity and images in individual cells. Many of these tools were pioneered by the NIH’s Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative®. The researchers identified many additional changes in brains beyond the usual molecular signature known to scientists: buildup of a protein called tau in nerve cells next to small blood vessels deep in the brain’s folds.
For example, the researchers found a striking 56% loss of a specific type of neurons in that particular brain area, which takes hard hits during impacts and also where the tau protein accumulates. This loss was evident even in athletes who had no tau buildup. It also tracked with the number of years of exposure to repetitive head impacts. The findings thus suggest that neuronal damage can occur much earlier than is visible by the currently known CTE disease marker tau. The team also observed that the brain’s immune cells, called microglia, became increasingly activated in proportion to the number of years the athletes had played contact sports.
The study also revealed important molecular changes in the brain’s blood vessels. These changes included gene patterns that could signal immune activity, a possible reaction to lower oxygen levels in nearby brain tissue, and thickening and growth of small blood vessels. Together with these findings, the researchers identified a newly described communication pathway between microglia and blood vessel cells. The authors suggest that this crosstalk may help explain how early cellular problems set the stage for disease progression long before CTE becomes visible.
The study is one of the first to focus on younger athletes, shifting attention from advanced CTE in older people to the earliest cellular signatures of damage.
“What’s striking is the dramatic cellular changes, including significant, location-specific neuron loss in young athletes who had no detectable CTE,” said Richard Hodes, M.D., director of NIH’s National Institute on Aging (NIA). “Understanding these early events may help us protect young athletes today as well as reduce risks for dementia in the future.”
By revealing the earliest cellular warning signs, this work lays the foundation for new ways to detect brain effects of repetitive head injuries and potentially lead to interventions that could prevent devastating CTE neurodegeneration.
This research was supported by NINDS and NIA through grants F31NS132407, U19AG068753, RF1AG057902, R01AG062348, R01AG090553, U54NS115266, and P30AG072978.
About the National Institute of Neurological Disorders and Stroke (NINDS): NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. https://www.ninds.nih.gov/
About the National Institute on Aging (NIA): NIA seeks to understand the nature of aging and diseases associated with growing older, with the goal of extending the healthy, active years of life. https://www.nia.nih.gov
About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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Reference
Butler MLMD, Pervaiz N, Breen K. et al. Repeated head trauma causes neuron loss and inflammation in young athletes. Nature (2025). DOI: 10.1038/s41586-025-09534-6